Histologically confirmed hippocampal structural features revealed by 3T MR imaging: potential to increase diagnostic specificity of mesial temporal sclerosis.

BACKGROUND AND PURPOSE: With appropriate selection, temporal lobe epilepsy is potentially curable with surgical intervention achieving seizure freedom in ~80% of individuals. MR imaging-based identification of MTS remains central to the selection process but currently relies on qualitative visual analysis. We sought to determine if new ultrastructural hippocampal details seen on 3T MR imaging had histopathologic correlates and whether these could serve as a useful tool in MTS identification. MATERIALS AND METHODS: Patients undergoing selective anterior temporal lobectomy (n = 5) were scanned using 3T MR imaging preoperatively. En bloc resections were rescanned and subsequently prepared for histopathologic analysis of all hippocampal layers in the CA1-3 regions. Using a newly identified landmark from 3T FSTIR coronal images in 20 patients with histologically confirmed MTS, blinded studies compared ipsilateral and contralateral sides to generate threshold measurements for application in a fast quantitative analysis tool. RESULTS: Histopathologic analysis and correlation with 3T imaging of en bloc resections identified the low-intensity signal as the stratum lacunosum. MTS was associated with extensive gliosis throughout the CA1-3 regions, with loss of tissue thickness in the stratum pyramidale most pronounced in CA1. Fast quantitative analysis by using the stratum lacunosum as a landmark provided a test that identifies MTS with a SN of 70% and SP of 85%. CONCLUSIONS: Here we delineated ultrastructural hippocampal details seen on 3T MR imaging in both the in vivo and ex vivo setting, correlating these with histopathologic features consistent with MTS, and provided preliminary data suggesting their utility in the development of a quantitative analysis assessment tool for application in surgical-candidate selection.

Ensembl 2008.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Dermatofibrosarcoma protuberans in two patients with acquired immunodeficiency syndrome.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous tumor of intermediate malignancy. Most commonly, it arises as an asymptomatic, indurated plaque on the trunk within which protuberant nodules develop over time. We describe its occurrence in two patients with human immunodeficiency virus, a previously unreported association. The first patient, a 41-year-old woman, complained of painful lesions around the left shoulder that developed within a scar from previous trauma to the area. The second patient, a 50-year-old man, developed a recurrent DFSP within the scar from a previous surgical procedure. Dermatofibrosarcoma protuberans was confirmed in both cases by the histopathologic and immunohistochemical findings.

The Pfam protein families database.

Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the WWW in the UK at http://www.sanger.ac.uk/Software/Pfam/, in Sweden at http://www.cgr.ki.se/Pfam/ and in the US at http://pfam.wustl.edu/. The latest version (4.3) of Pfam contains 1815 families. These Pfam families match 63% of proteins in SWISS-PROT 37 and TrEMBL 9. For complete genomes Pfam currently matches up to half of the proteins. Genomic DNA can be directly searched against the Pfam library using the Wise2 package.